rs1805414

Positions:

• chr1-226385663-A-G
• chr1-226385663-A-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001618.4(PARP1):​c.852T>C​(p.Ala284=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 1,612,866 control chromosomes in the GnomAD database, including 115,585 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.42 (14757 hom., cov: 33)
  • Exomes 𝑓: 0.36 (100828 hom.)
• Consequence: PARP1 NM_001618.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.58

Genes affected

PARP1 (HGNC:270): (poly(ADP-ribose) polymerase 1) This gene encodes a chromatin-associated enzyme, poly(ADP-ribosyl)transferase, which modifies various nuclear proteins by poly(ADP-ribosyl)ation. The modification is dependent on DNA and is involved in the regulation of various important cellular processes such as differentiation, proliferation, and tumor transformation and also in the regulation of the molecular events involved in the recovery of cell from DNA damage. In addition, this enzyme may be the site of mutation in Fanconi anemia, and may participate in the pathophysiology of type I diabetes. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP7: Synonymous conserved (PhyloP=-2.58 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PARP1	NM_001618.4	c.852T>C	p.Ala284=	synonymous_variant	7/23	ENST00000366794.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARP1	ENST00000366794.10	c.852T>C	p.Ala284=	synonymous_variant	7/23	1	NM_001618.4	P1

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64471 AN: 151942 Hom.: 14726 Cov.: 33

Gnomad AFR AF: 0.542

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.806

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.396

GnomAD3 exomes AF: 0.426 AC: 107127 AN: 251338 Hom.: 25452 AF XY: 0.413 AC XY: 56066 AN XY: 135860

Gnomad AFR exome AF: 0.553

Gnomad AMR exome AF: 0.554

Gnomad ASJ exome AF: 0.334

Gnomad EAS exome AF: 0.813

Gnomad SAS exome AF: 0.365

Gnomad FIN exome AF: 0.408

Gnomad NFE exome AF: 0.338

Gnomad OTH exome AF: 0.376

GnomAD4 exome AF: 0.358 AC: 523678 AN: 1460806 Hom.: 100828 Cov.: 38 AF XY: 0.357 AC XY: 259707 AN XY: 726764

Gnomad4 AFR exome AF: 0.559

Gnomad4 AMR exome AF: 0.538

Gnomad4 ASJ exome AF: 0.330

Gnomad4 EAS exome AF: 0.793

Gnomad4 SAS exome AF: 0.369

Gnomad4 FIN exome AF: 0.403

Gnomad4 NFE exome AF: 0.327

Gnomad4 OTH exome AF: 0.377

GnomAD4 genome AF: 0.425 AC: 64564 AN: 152060 Hom.: 14757 Cov.: 33 AF XY: 0.429 AC XY: 31862 AN XY: 74320

Gnomad4 AFR AF: 0.543

Gnomad4 AMR AF: 0.458

Gnomad4 ASJ AF: 0.328

Gnomad4 EAS AF: 0.807

Gnomad4 SAS AF: 0.380

Gnomad4 FIN AF: 0.401

Gnomad4 NFE AF: 0.332

Gnomad4 OTH AF: 0.396

Alfa AF: 0.361 Hom.: 6098

Bravo AF: 0.439

Asia WGS AF: 0.546 AC: 1900 AN: 3478

EpiCase AF: 0.320

EpiControl AF: 0.326

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.037
DANN	Benign	0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1805414; hg19: chr1-226573364; COSMIC: COSV64689261; COSMIC: COSV64689261;